The goal of both components of this proposal is to evaluate methods which may lead to reduction in the occurrence of intracranial hemorrhages in very low birth weight infants (VLBWI), and perhaps thereby, to reduce the risk of later handicaps in these children. Project 1 is a clinical trial of phenobarbital prophylaxis, and project 2 is a case-control study of selected intracranial hemorrhages in VLBWI. Project 1, which was initiated in June, 1981, is restricted to babies weighing less than 1,751 grams at birth, who require intubation, and who do not have any evidence of intra-cranial hemorrhage on ultrasonogram performed within the first twelve hours of life. These babies are randomly assigned to receive intravenously either phenobarbital in a loading does of 20mgm/kgm within twelve hours of birth and a maintenance dose of 5mgm/kgm/day for five days, or a placebo during the same time span. Follow-up ultrasonograms will be obtained between the seventh and tenth day of life. The anticipated sample size should allow appreciation of a 50 percent reduction in the occurrence of intracranial hemmorhages with a probability of .9. Subjects recruited for project 2 will have been admitted to the neonatal intensive care unit at Children's Hospital and the Brigham and Women's Hospital, weigh less than 1,750 grams at birth, and had an ultrasonogram. Cases will have documented germinal matrix hemorrhage (GMH) and controls of the same gender and similar age will have sonographic evidence of no GMH. Data about risk factors and perinatal variables will be obtained from hospital charts, and from interviews of mothers. Many of the hypotheses to be tested were generated in epidemiologic studies of babies who died. These hypotheses concern demographic variables, the mother's medical and reproductive history, as well as nutrition and drug exposure during pregnancy. Data analysis will include mulivariate techniques.